The trial met the primary endpoint of safety, defined as no more than 25% of postmenopausal patients showing an E2 level more than 10 pg/mL above their baseline value on two or more consecutive tests taken at least 2 weeks apart, say Michelle Melisko, from the University of California–San Francisco, USA, and co-workers.

However, the investigators note in JAMA Oncology the “surprising” finding that baseline E2 elevation was “common and complicates this assessment”. Indeed, E2 was above 10 pg/mL in 37% of the 76 women with hormone receptor-positive, stage I–III breast cancer.

Nevertheless, persistent E2 elevation above baseline occurred in none of the 40 patients who were given a vaginal ring delivering 7.5 μg/day for 12 weeks and in just 12% of the 34 women who used 1% IVT for 12 weeks, beginning with a 0.5 mg/day dose and, after 2 weeks, switching to a 0.5 mg dose three times a week.

Transient elevation was detected in 11% of the patients with a vaginal ring and 12% of those using IVT, the researchers say.

And gynaecological examination and sexual quality of life questionnaires completed at baseline and 12 weeks indicated that all patients experienced improvements in vaginal atrophy, sexual interest and dysfunction.

“For patients who experience symptomatic improvement on either an estradiol-releasing vaginal ring or IVT, our current standard clinical practice is to continue on therapy with measurements of serum E2 every few months depending on patient preferences”, the authors therefore conclude.

The authors of an accompanying editorial caution, however, that there is “no evidence” to show “whether the study threshold of less than 25% persistent elevation in estradiol, or any other level of elevation, is ‘safe’ for breast cancer survivors, in the sense of having no effect on their risk of future breast cancer events.”

But Katherine Reeder-Hayes and Hyman Muss, from the University of North Carolina, Chapel Hill, USA, admit that the “good news” of symptom improvements in all patients given a vaginal ring or IVT is “clearly underscoring the quality of life benefits for both of these treatments.”

And while awaiting further research on the risk of vaginal hormone intervention in the context of the diminishing benefits of continuing AI therapy over time for many breast cancer survivors , they conclude: “[I]f nonhormonal approaches are initially considered and found to be unhelpful and after a frank discussion and shared decision making, the interventions such as those proposed by Drs. Melisko and colleagues that may have a meaningful effect on quality of life, relationship satisfaction, and ability to move on beyond breast cancer, appears the best strategy.”